Last week, Roche and Genentech announced results from its Phase III trial of trastuzumab emtansine (T-DM1) which slows progress of metastatic breast cancer, they hope to have FDA approval later in the year.

In further news, Perjeta, also for treating breast cancer, has been given FDA approval also for treating HER2-postive late-stage (metastatic) breast cancer.

Perjeta is meant for patients that have not previously been treated for metastatic breast cancer with an anti-HER2 therapy or chemotherapy. The HER2 protein is involved in normal cell growth but is seen to increase in some types of cancer boosting cell growth rate and survival odds and making it more stubborn to treat the cancer.

Perjeta is given in combination with trastuzumab an anti-HER2 therapy, and docetaxel, a type of chemotherapy. The trastuzumab emtansine (T-DM1) version that is still awaiting approval combines the chemo therapy with a system to deliver the drug directly inside the cancer cells, making it more effective.

Perjeta is a humanized monoclonal antibody, manufactured through biotechnology methods. Administered intravenously, it appears to work by targeting a different part of the HER-protein than trastuzumab, resulting in further reduction in growth and survival of HER2-positive breast cancer cells.

Unfortunately Genentech has experienced some production issues with the drug, so the FDA has limited its approval to product that has not been affected by the supply issues, which could potentially reduce long term supplies in the future.

Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research clarified the FDA decision:

“Given the need for additional treatments for metastatic breast cancer, we made the decision to approve this drug today and not to delay its availability to patients pending resolution of the production issues relating to future supply … Genentech is currently developing a plan to mitigate the effect on patients of any potential shortage of Perjeta.”

This year, an estimated 226,870 women will be diagnosed with breast cancer, and 39,510 will die from the disease. About 20 percent of breast cancers have increased amounts of the HER2 protein. Breast cancer remains the second leading cause of cancer-related death among women.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research continues that:

“Since trastuzumab was first approved more than a decade ago, continued research has allowed us to better understand the role HER2 plays in breast cancer … This research provided the background to combine two targeted drugs trastuzumab and Perjeta with docetaxel to slow disease progression in breast cancer.”

A single clinical trial to study the safety and effectiveness of Perjeta was conducted involving 808 patients with HER2-positive metastatic breast cancer. They were tested prior to treatment to determine if their HER2 protein was increased. Patients were then assigned randomly to receive Perjeta, trastuzumab and docetaxel or trastuzumab and docetaxel with a placebo.

The purpose of the study was to measure the length of time a patient lived without the cancer progressing, progression-free survival (PFS). Those patients that were treated with the combination containing Perjeta had a median PFS of 18.5 months, while those treated with the combination containing placebo had greatly reduced PFS of only 12.4 months.

The most common side effects observed in patients receiving Perjeta in combination with trastuzumab and docetaxel were diarrhea, hair loss, a decrease in infection-fighting white blood cells, nausea, fatigue, rash, and nerve damage (peripheral sensory neuropathy). With this in mind, Perjeta is being approved with a Boxed Warning alerting patients and health care professionals to the potential risk of death or severe effects to a fetus. Pregnancy status must be verified prior to the start of Perjeta treatment.

The therapy was reviewed under the agency’s priority review program, which provides for an expedited six-month review of drugs that may offer major advances in treatment. Clearly an increased PFS time of nearly some 50% is a major improvement and if the FDA bring trastuzumab emtansine (T-DM1) into play later in the year, we may see that number increase again.

Written by Rupert Shepherd